The present invention relates to an orally administrable cholesterol lowering agent and, more particularly, to an orally administrable cholesterol lowering agent which is superior in compressing shapability, stability under a moistening environment, and fluidity together with an easiness of swallowing.
Conventionally, anion exchange resins are large in dose and hence tablets become large. Considering swallowability, capsule-shaped tablets are preferable. For the capsule-shaped tablets, however, a part of a punch may be deformed upon compressing unlike circular tablets, and the punch is more likely to be broken. In methods of compressing with a certain volume of water contained that are conventionally made (Japanese Patent Application Laid-Open Nos. 2-286621 and 3-236326), a larger compressing pressure is required and are thus insufficient as methods of preparing plain tablets.
On the other hand, regarding the coating of tablets containing an anion exchange resin as an active component, such a method is known that uses cholestyramin resin and dissolves with heat stearic acid into polyethylene glycol for coating without using a solvent (Japanese Patent Application Laid-Open No. 3-236326). Tablets coated by this method are, however, inferior in storage stability in an open condition. The tablets are hygroscopically disintegrated in several hours at a room temperature. Accordingly, the tablets have only a poor stability after packaging is opened. In addition, a coating layer has a low strength and is greatly worn. The tablets may thus be broken in the packaging process or during transportation.
Commercially available cholestyramins are dry syrups dissolved on use and are desired to be formed into tablets considering the easiness of swallowing and handling. Favorable tablets have not been obtained yet because of the above mentioned reasons.
The present inventors have found a method for coating an anion exchange resin with hydroxypropylcellulose (Japanese Patent Application No. 4-320155). While the stability in a moistening environment of them is improved, the tablets coated by this method have, however, the disadvantage that the fluidity is lost with the tablets being adhered to each other because the hydroxypropylcellulose used as the coating layer absorbs water to increase the viscosity.
The present inventors had made tremendous studies and considerations with respect to the above mentfoned problems. As a result, it has been found that the compressing shapability can be improved significantly by using an anion exchange resin as an active component and containing, as secondary components a certain amount of water and silicon dioxide that is used as a fluidity imparting agent. It has also been found that such an orally administrable cholesterol lowering agent which is superior in easiness of swallowing, stability in a moistening environment, and maintenance of fluidity is obtained by coating plain tablets with hydroxypropylmethylcellulose having a higher viscosity than those commonly used.